Zhongqian Su, Yuxiang Li, Fangchao Tong, Yiying Cai, Yuanfang Li, Jing Ding, Qiang Wang, Xin Wang
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引用次数: 0
摘要
目的：通过匹罗卡品诱导的大鼠癫痫模型，探讨CRMP2在苔藓纤维发芽（MFS）中的作用。方法：首先在注射匹罗卡品后1、7、14、28 d处死大鼠。采用实时荧光定量PCR （qPCR）和Western blot （WB）检测海马和皮层mRNA和蛋白水平。接下来，将shCRMP2 AAV注入海马齿状回，以降低CRMP2的表达。2周后，注射匹罗卡品致痫大鼠模型。在癫痫持续状态（SE）诱导当天，shCtrl + EP + LCM组和shCRMP2 + EP + LCM组动物每天2次灌胃拉科沙胺（LCM）。第7 ~ 28天对大鼠进行视频监测，注射匹罗卡品后第28天处死，进行后续实验。结果：在本研究中，我们观察到癫痫大鼠海马中磷酸化的CRMP2下调。此外，LCM处理降低了这些大鼠海马中CRMP2蛋白的表达水平。CRMP2敲除和LCM治疗均可降低癫痫大鼠齿状回苔藓纤维发芽（MFS），缩短癫痫发作持续时间。此外，我们发现癫痫大鼠海马的微管动力学降低。CRMP2敲除和LCM治疗均可增加癫痫大鼠海马的微管动力学。结论：在匹罗卡品诱导的大鼠癫痫模型中，我们令人信服地证明了CRMP2调节苔藓纤维发芽和调节微管动力学。
CRMP2 regulates mossy fiber sprouting and modulates microtubule dynamics in a pilocarpine induced rat model of epilepsy.
Objective: Our study aimed to investigate the role of CRMP2 in mossy fiber sprouting (MFS) using a pilocarpine-induced rat model of epilepsy.
Methods: First, the rats were sacrificed on the 1, 7, 14 and 28 day after pilocarpine injection. Quantitative Real-time PCR (qPCR) and Western blot (WB) were performed to assess mRNA and protein levels in the hippocampus and cortex. Next, shCRMP2 AAV was injected into the dentate gyrus of hippocampus to knock down CRMP2 expression. Two weeks later, the epileptic rat model was induced by pilocarpine injection. On the day of status epilepticus (SE) induction, animals in the shCtrl + EP + LCM and shCRMP2 + EP + LCM group received twice-daily intragastric administration of Lacosamide (LCM). The rats were video monitored from day 7 to 28, and were sacrificed on day 28 after pilocarpine injection for subsequent experiment.
Results: In the present study, we observed downregulation of phosphorylated CRMP2 in the hippocampus of epileptic rats. Additionally, LCM treatment reduces the expression level of CRMP2 protein in the hippocampus of these rats. Both CRMP2 knockdown and LCM treatment were found to decrease mossy fiber sprouting (MFS) in the dentate gyrus and shorten the duration of seizures in epileptic rats. Furthermore, we discovered that microtubule dynamics are reduced in the hippocampus of epileptic rats. Both CRMP2 Knockdown and LCM treatment were shown to increase the microtubule dynamics in the hippocampus of rats with epilepsy.
Conclusion: In conclusion, we demonstrated convincingly that CRMP2 regulates mossy fiber sprouting and modulates microtubule dynamics in a pilocarpine induced rat model of epilepsy.
期刊介绍：
An international multidisciplinary journal devoted to fundamental research in the brain sciences.
Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed.
With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.
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